This project will determine the conformation of specific carcinogens adducted to DNA. Adducts of styrene and of the polycyclic aromatic hydrocarbons benzo[a]pyrene, benzo[c]phenanthrene, benz[a]anthracene, and dimethylbenz[a]anthracene will be examined within the context of the human N-ras protooncogene sequences at codons 12 and 61. These sequences have been chosen because carcinogenesis induced by these compounds is correlated with adduct formation in these sequences, leading to point mutations which result in oncogene activation. The specific aims are to investigate how adduct structure influences conformation, to determine how regioisomers of the same adduct differ in conformation, and to determine how sequence isomers of the same adduct differ in conformation. This will enable controversies regarding the conformation of polycyclic aromatic hydrocarbon adducts in DNA to be resolved. Propanoguanosine adducts will be used as models for the pyrimidopurinone adducts formed by malondialhyde which induces frameshift mutations. These will be examined in a frameshift-prone sequence derived from the hisD3052 tester strain of S. typhimurium. The mechanism of ethylene dibromide-induced mutagenesis will be studied by examination of oligodeoxynucleotides containing s-[2-(N7-guanyl)ethyl]thiol derivatives, which represent the major DNA adduct formed by this compound. This will enable adduct conformation to be compared with biologic response.